A Study of AK104 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer

NCT ID: NCT04647344

Last Updated: 2024-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-24
• Study Completion Date: 2023-12-31

Brief Summary

This is a phase Ib/II , open-label, multicenter single arm study designed to evaluate the efficacy, safety, tolerability, pharmacokinetic (PK), and immunogenicity of AK104 combined with Carboplatin and Pemetrexed/ Paclitaxel as first-line therapy in patients with locally advanced or metastatic non-small cell lung cancer.

Conditions

Lung Cancer Non-Small Cell Stage IIIB/IIIC/IV

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nonsquamous NSCLC

Group Type: EXPERIMENTAL

AK104 plus Carboplatin and Pemetrexed

Intervention Type: DRUG

Subjects receive AK104 15mg/kg intravenously (IV) plus pemetrexed 500 mg/m\^2 IV and carboplatin area under the curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK104 15mg/kg IV plus pemetrexed 500 mg/m\^2 IV Q3W until progression.

Squamous NSCLC

Group Type: EXPERIMENTAL

AK104 plus Carboplatin and paclitaxel

Intervention Type: DRUG

Subjects receive AK104 15mg/kg intravenously (IV) plus paclitaxel 175 mg/m\^2 IV and carboplatin area under the curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK104 15mg/kg IV IV Q3W until progression.

Interventions

AK104 plus Carboplatin and Pemetrexed

Subjects receive AK104 15mg/kg intravenously (IV) plus pemetrexed 500 mg/m\^2 IV and carboplatin area under the curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK104 15mg/kg IV plus pemetrexed 500 mg/m\^2 IV Q3W until progression.

Intervention Type: DRUG

AK104 plus Carboplatin and paclitaxel

Subjects receive AK104 15mg/kg intravenously (IV) plus paclitaxel 175 mg/m\^2 IV and carboplatin area under the curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK104 15mg/kg IV IV Q3W until progression.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed written informed consent form voluntarily.
• Age over 18 years old (inclusive) and not more than 75 years old (inclusive), when signing the informed consent form.
• Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
• Expected life expectance ≥ 3 months.
• Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC.
• No prior systemic chemotherapy for advanced or metastatic NSCLC. Subjects who have received prior adjuvant chemotherapy or neoadjuvant chemotherapy with curative intent, or definitive chemoradiotherapy for advanced disease, will be eligible provided that progression has occurred >6 months from last treatment.
• At least one measurable tumor lesion per RECIST 1.1 criteria. A lesion previously irradiated will not be considered a target lesion.
• Subjects must provide an available tumor tissue sample taken < 1 year prior to first dose of study treatment.
• Subjects must provide wild-type epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) reported by tissue-based tests（for non-squamous NSCLC subjects only）.
• Adequate organ function.
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception.
• nonsterilized males who are sexually active with a female partner of childbearing potential must use highly effective method of contraception from Day 1 and for 120 days after the last dose of investigational product.

Exclusion Criteria

• Subjects who are diagnosed as NSCLC that harbors an epidermal growth factor receptor (EGFR)-sensitizing mutation or anaplastic lymphoma kinase (ALK) gene translocation.
• Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the subject is ineligible
• Received prior treatment with EGFR inhibitors or ALK inhibitors.
• Is currently participating intervention study or has participated in a study of an investigational agent or investigational device within 4 weeks prior to administration of AK104.
• Prior exposure to any anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody, or any other antibody or drug therapy for T cell co-stimulatory or checkpoint pathways, such as Inducible T-cell co-stimulator (ICOS) or agonists (e.g. CD40, CD137, GITR and OX40 etc).
• Subjects who received non-thoracic radiotherapy >30 Gy within 4 weeks prior to the first dose , or thoracic radiotherapy >30 Gy within 24 weeks prior to the first dose study drug.
• Other active malignancies within 2 years, except for locally treatable (manifested as cured) malignancies, such as basal or skin squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ.
• Subjects with active, known or suspected autoimmune disease, or a medical history of autoimmune disease,
• Subjects who require systemic corticosteroids (a dose equivalent to >10 mg/day prednisone) or other immunosuppressive drugs within 14 days prior to administration of AK104.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Active or previously documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis or chronic diarrhea).
• Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
• Known history of active tuberculosis (TB).
• An active infection requiring systemic therapy.
• Subjects with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) DNA exceeding 1000 IU/ mL or active hepatitis C virus (HCV) should be excluded. Subjects with non-active HBsAg carriers, treated and stable hepatitis B (HBV DNA <1000 IU/ mL) , and cured hepatitis C can be enrolled. Subjects with positive HCV antibodies are eligible only if the HCV RNA test results are negative.
• Known history of testing positive for human immunodeficiency virus (HIV).
• Presence of meningeal metastasis, spinal cord compression, leptomeningeal disease or active brain metastasis.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Receipt of live vaccination within 30 days of planned treatment start, or plan to receive live vaccine during the study.
• Known history of server hypersensitivity to other monoclonal antibodies.
• Known severe allergic reactions to pemetrexed, paclitaxel, carboplatin or platinum-containing component, or their preventive medications.
• Known allergic reactions to any ingredients of AK104.
• Known history of substance abuse, or alcohol abuse
• Pregnant or lactating women.
• Any conditions that, in the investigator's opinion, may put subjects treated with the study drug at risks, or interfere with the evaluation of study drug or subject safety, or the interpretation of study results.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Akeso

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Li Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University Cancer Center, Guangzhou, China

Locations

Sun Yat-Sen University Cancer Center

Guanzhou, Guangdong, China

Countries

China

Other Identifiers

AK104-207

Identifier Type: -

Identifier Source: org_study_id